Breast cancer is the most frequently diagnosed cancer (excluding skin cancer) and the No. 2 cancer killer in U.S. women. Due to recent advances in medical imaging, efficient screening and early detection of breast cancer have resulted to lower morbidity from the disease. Because of the successful detection of breast cancer at an early stage, treatment techniques have also improved. The premise of ablation techniques is that, if a tumor and its normal-tissue margin can be destroyed in situ, instead of being removed, the impact on the disease should be equivalent. In addition, if the mortality associated with operative intervention can be avoided, then the outcome using localized treatments may be more advantageous. Ablation techniques are therefore slowly emerging as less invasive, but equally effective, in the treatment of early-stage breast cancer, with High- Intensity Focused Ultrasound (HIFU) being the only truly noninvasive, extracorporeal technique. The general objective of the proposed study is thus to optimize and assess the performance of the method of Harmonic Motion Imaging for Focused Ultrasound (HMIFU), an 1) entirely noninvasive (non-contact), 2) simple to implement, 3) real-time, 4) precise (estimating displacements of 1-10 microns), 5) fully integratable, and 6) low- cost technique for localized detection and in situ thermal treatment planning and monitoring of early-stage breast cancer. The underlying hypothesis is that the tumor has sufficiently distinct mechanical properties from the normal and ablated breast tissues so that the Harmonic Motion Imaging (HMI) technique can localize, treat and monitor the treatment of such a tumor. The specific aims of the proposed study are thus to: 1) Establish sensitivity and specificity of the HMI technique for tumor detection in experimental phantoms and ex vivo human breast specimens;2) Optimize the HMIFU technique for real-time monitoring and treatment in porcine liver specimens in vitro;and 3) Assess the HMIFU performance for tumor ablation monitoring in animal tumor models in vivo. Apart from the aforementioned advantages over alternative techniques and the high risk involved given the preliminary nature of the results shown, HMIFU may prove to be an important option to pre-menopausal and younger women, for whom early detection and treatment is most critical and who would benefit the most from a controlled, localized treatment that aims at sparing normal breast tissue. Most importantly, the high impact of this R21 application may lie in the fact that the same technique can easily be applied in deeper-seated tumors with fewer alternative treatment options, such as in abdominal, e.g., liver and the pancreatic cancers, preliminary feasibility of which will also be determined. An all-ultrasound method will be designed for detection and monitoring of tumor ablation in early-stage breast cancer. This will constitute a simple, low-cost, noninvasive and real-time method for simultaneous, fast and effective tumor detection and treatment. This new method may prove to be an important option offered to pre-menopausal and younger women, for whom early detection and treatment is most critical and who would benefit the most from a controlled, localized treatment that aims at sparing normal breast tissue.